Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host’s immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA.

Oral Probiotic Activities and Biosafety of Lactobacillus gasseri HHuMIN D

Background Specific probiotic bacteria may have inhibitory effects against oral pathogens. Lactobacillus spp. have been researched worldwide and are used in probiotics, but due to difficulties with laboratory cultivation of and experimentation on oral microorganisms, there are few reports of Lactobacillus spp. being isolated from the oral cavity and tested against oral pathogens. This research aimed to determine the safety and inhibitory impacts of L. gasseri HHuMIN D as a potential oral probiotic with biotherapeutic capabilities against oral pathogens. Results The microbial and genetic characteristics of L. gasseri HHuMIN D were evaluated in this research. A 5% dilution of L. gasseri HHuMIN D culture supernatant exhibited 88.8% inhibition against halitosis-producing anaerobic microorganisms and L. gasseri HHuMIN D exhibited powerful inhibitory effects on the growth of every harmful oral bacterium tested. Unfortunately, other oral bacteria affected the growth of L. gasseri HHuMIN D, suggesting a poor proliferative response to most co-cultures. Hydrogen peroxide production by L. gasseri HHuMIN D reached 802 µmol/L after 12 hours and gradually diminished until 24 hours. It efficiently aggregated with P. catoniae and S. sanguinis, and completely supressed S. mutans-manufactured artificial dental plaque. L. gasseri HHuMIN D’s KB cell adhesion capacity was 4.41 cells per cell, and the cell adhesion of F. nucleatum and S. mutans diminished strongly in protection and displacement assays. L. gasseri HHuMIN D was evaluated for safety using ammonia and biogenic amine development, hemolytic property and mucin degradation testing, antibiotic susceptibility, and whole genome sequencing (WGS). Conclusion Our results suggest that L. gasseri HHuMIN D may be a safe, bioactive, lactobacterial food ingredient, starter culture, and/or probiotic microorganism for human oral health.

LDOC1 Suppresses Microbe-Induced Production of IL-1β in Human Normal and Cancerous Oral Cells through the PI3K/Akt/GSK-3β Axis

Poor oral hygiene (POH) is associated with oral squamous cell carcinoma (OSCC). Oral microbes often proliferate due to POH. Array data show that LDOC1 plays a role in immunity against pathogens. We investigated whether LDOC1 regulates the production of oral microbe-induced IL-1β, an oncogenic proinflammatory cytokine in OSCC. We demonstrated the presence of Candida albicans (CA) in 11.3% of OSCC tissues (n = 80). CA and the oral bacterium Fusobacterium nucleatum stimulate higher levels of IL-1β secretion by LDOC1-deficient OSCC cells than by LDOC1-expressing oral cells. CA SC5314 increased OSCC incidence in 4-NQO (a synthetic tobacco carcinogen) and arecoline-cotreated mice. Loss and gain of LDOC1 function significantly increased and decreased, respectively, CA SC5314-induced IL-1β production in oral and OSCC cell lines. Mechanistic studies showed that LDOC1 deficiency increased active phosphorylated Akt upon CA SC5314 stimulation and subsequent inhibitory phosphorylation of GSK-3βS9 by activated Akt. PI3K and Akt inhibitors and expression of the constitutively active mutant GSK-3βS9A significantly reduced the CA SC5314-stimulated IL-1β production in LDOC1-deficient cells. These results indicate that the PI3K/Akt/pGSK-3β signaling pathway contributes to LDOC1-mediated inhibition of oral microbe-induced IL-1β production, suggesting that LDOC1 may determine the pathogenic role of oral microbes in POH-associated OSCC.

A sticky situation: a case of <i>Actinomyces viscosus</i> vertebral osteomyelitis

Actinomyces viscosus is an oral bacterium that is rarely virulent in humans, with most case presentations involving dental and maxillofacial infections. We describe the first reported case of A. viscosus vertebral osteomyelitis in a patient who had a significant response to penicillin after minimal response to cephalosporin therapy.

Bacterial invaders drive CRC progression

The oral bacterium Fusobacterium nucleatum is often found in colorectal cancer (CRC). In the 21 July 2020 issue of Science Signaling, Casasanta et al. show that CRC cell–resident F. nucleatum promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients.

The Role of Porphyromonas gingivalis Virulence Factors in Periodontitis Immunopathogenesis

Porphyromonas gingivalis is an anaerobic Gram-negative oral bacterium involved in the pathogenesis of periodontitis. Periodontitis is an infection that is characterized by damage to the supporting tissues of the teeth so that it can cause tooth loss if not given treatment. P. gingivalis locally can invade periodontal tissue and avoid host defense mechanisms. This bacterium has virulence factors which can cause deregulation of innate immune responses and inflammation in the host. The role of P. gingivalis virulence factors such as capsules, fimbriae, lipopolysaccharides, and gingipain in the pathogenesis of periodontitis will be discussed in this paper.